The scientific objective of this proposal is to develop judiciously designed novel monomers which when formulated into a dental adhesive will drastically improve the adhesive/dentin bonding, thus significantly extending the longevity of resin-based tooth restorations. Click chemistry plays an essential role in the design and synthesis of the targeted novel monomers as the modular synthetic approach centers on the ability of click chemistry to link organic components together selectively and efficiently under mild conditions without affecting sensitive functional groups carried by each organic component. The proposed research stems from the critical challenge long facing restorative dentistry: dental restorations based on composite resins have a prohibitively high failure rate. One primary reason for the premature failure is the lack of a tight and long-lasting seal between the composite resin and the underline dentin. The inability of the current state-of-the-art dental adhesives to form a tight adhesive/dentin (a/d) seal is due to three major factors. First, the bonding between resin and dentin collagen, which relies on the infiltration and subsequent entanglement of resin polymers with exposed collagen fibrils, is poor. The micromechanical interlocking mechanism is intrinsically problematic as insufficient penetration, incomplete polymerization and solvent swelling all prohibit the formation of a tight a/d bonding. Second, the stability and mechanical strength of the exposed/unprotected dentin collagen is often low. When the foundation to which composite resins adhere is itself shaky, achieving long-lasting restoration is not just challenging, but impossible. Third, the strength of infiltrated resin polymers is usually poor due chiefly to the incomplete polymerization of current monomers under aqueous environment. In this proposal, novel monomers designed to address all three critical issues simultaneously will be synthesized using "click chemistry". Such monomers have the following unique features: 1) They have a number of hydrolytically stable polymerizable methacrylamide groups, ensuring high monomer/polymer conversion;2) They include protected aldehyde groups which can be hydrolytically deprotected and subsequently crosslink exposed collagen, thus significantly enhancing the collage biostability and mechanical strength;3) Hydrolytic deprotection of aldehydes yields hydrophilic resin branches, which facilitate resin permeation to hydrated collagen and produces no breakaway small molecules;and 4) Crosslinked collagen is covalently bonded to resin, creating a tight and stable a/d bond. Innovative techniques, including FTIR and micro-Raman chemical imaging, tensile strength testing, etc will be utilized to thoroughly characterize how the newly designed monomer-based adhesives polymerize and interact with dentin. The goal is not only to confirm that the design principles and the synthesized monomers work, but also to gain deep understanding into how and why they do. PUBLIC HEALTH RELEVANCE: The proposed research, if successfully carried out, will significantly increase the lifetime of resin based tooth restorations, thus positively impact the public health. It will also benefit the environment as the resin based restoration will gain additional advantage over amalgam.